Mesenchymal Stem Cell-Derived Exosomes Ameliorate Delayed Neurocognitive Recovery in Aged Mice by Inhibiting Hippocampus Ferroptosis via Activating SIRT1/Nrf2/HO-1 Signaling Pathway DOI Creative Commons
Jie Liu, Jingyao Huang, Zhenjiang Zhang

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 22

Published: Sept. 30, 2022

Delayed neurocognitive recovery (dNCR) is a prevalent perioperative neurological complication in older patients and has common characteristics such as acute cognitive dysfunction, impaired memory, inattention. Mesenchymal stem cell-derived exosomes (MSCs-Exo) are enclosed by lipid bilayer contain proteins, DNA, miRNA, other components, which important mediators of intercellular communication. It been reported that could play an role the treatment neurodegenerative diseases, nerve injury, diseases. In this study, we examined effects MSCs-Exo on dNCR aged mice after exploratory laparotomy evaluated their potential regulatory mechanisms. We found ameliorated impairment mice. inhibit hippocampus ferroptosis increase expression silent information regulator 1 (SIRT1), factor nuclear factor-erythroid 2-related 2 (Nrf2), heme oxygenase-1 (HO-1) Interestingly, above were abolished SIRT1 selective inhibitor EX-527. conclusion, these findings indicated can ameliorate inhibiting via activating SIRT1/Nrf2/HO-1 signaling pathway, providing avenue for dNCR.

Language: Английский

Molecular mechanisms of ferroptosis and relevance to inflammation DOI Open Access

Liyan Deng,

Shasha He,

Nuoqing Guo

et al.

Inflammation Research, Journal Year: 2022, Volume and Issue: 72(2), P. 281 - 299

Published: Dec. 19, 2022

Language: Английский

Citations

142
A Novel Anti-Osteoporosis Mechanism of VK2: Interfering with Ferroptosis via AMPK/SIRT1 Pathway in Type 2 Diabetic Osteoporosis DOI
Chen Jin,

Kai Tan,

Zhe Yao

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(6), P. 2745 - 2761

Published: Jan. 31, 2023

Type 2 diabetic osteoporosis (T2DOP) is a chronic bone metabolic disease. Compared with traditional menopausal osteoporosis, the long-term high glucose (HG) microenvironment increases patients' risk of fracture and osteonecrosis. We were accumulating evidence that implicated ferroptosis as pivotal mechanism glucolipotoxicity-mediated death osteocytes osteoblast, novel form programmed cell resulting from uncontrolled lipid peroxidation depending on iron. Vitamin K2 (VK2), fat-soluble vitamin, clinically applied to prevent improve coagulation. This study aimed clarify role VK2 in HG-mediated ferroptosis. established mouse T2DOP model by intraperitoneal injection streptozotocin solution high-fat high-sugar diet. also cultured marrow mesenchymal stem cells (BMSCs) HG simulate environment vitro. Based our data, inhibited loss ferroptosis, latter manifested decreased levels mitochondrial reactive oxygen species, peroxidation, malondialdehyde increased glutathione In addition, treatment was capable restoring mass strengthening expression SIRT1, GPX4, osteogenic markers distal femurs. As for further exploration, we found could activate AMPK/SIRT1 signaling, knockdown SIRT1 siRNA prevented VK2-mediated positive effect HG-cultured BMSCs. Summarily, ameliorate through activation signaling pathway inhibit

Language: Английский

Citations

62
GPX4, ferroptosis, and diseases DOI Open Access

Wangzheqi Zhang,

Yang Liu,

Liao Yan

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116512 - 116512

Published: April 3, 2024

GPX4 (Glutathione peroxidase 4) serves as a crucial intracellular regulatory factor, participating in various physiological processes and playing significant role maintaining the redox homeostasis within body. Ferroptosis, form of iron-dependent non-apoptotic cell death, has gained considerable attention recent years due to its involvement multiple pathological processes. is closely associated with ferroptosis functions primary inhibitor this process. Together, contribute pathophysiology several diseases, including sepsis, nervous system ischemia reperfusion injury, cardiovascular cancer. This review comprehensively explores roles impacts development progression these aim providing insights for identifying potential therapeutic strategies future.

Language: Английский

Citations

62
Pharmacological inhibition of ferroptosis as a therapeutic target for sepsis-associated organ damage DOI
Liang Huo, Chunfeng Liu,

Yujun Yuan

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 257, P. 115438 - 115438

Published: May 13, 2023

Language: Английский

Citations

54
Irisin attenuates type 1 diabetic cardiomyopathy by anti-ferroptosis via SIRT1-mediated deacetylation of p53 DOI Creative Commons

Yuan-juan Tang,

Zhen Zhang, Yan Tong

et al.

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: April 2, 2024

Abstract Background Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 1 diabetes mellitus (T1DM), which still lacks adequate therapy. Irisin, cleavage peptide off fibronectin III domain-containing 5, has been shown to preserve cardiac function ischemia–reperfusion injury. Whether or not irisin plays cardioprotective role DCM known. Methods and results T1DM was induced by multiple low-dose intraperitoneal injections of streptozotocin (STZ). Our current study showed that expression/level lower the heart serum mice STZ-induced TIDM. Irisin supplementation injection improved impaired DCM, ascribed inhibition ferroptosis, because increased associated malondialdehyde (MDA), decreased reduced glutathione (GSH) protein expressions solute carrier family 7 member 11 (SLC7A11) peroxidase 4 (GPX4), ameliorated irisin. In presence erastin, ferroptosis inducer, irisin-mediated protective effects were blocked. Mechanistically, treatment Sirtuin (SIRT1) p53 K382 acetylation, expression increasing its degradation, consequently upregulated SLC7A11 GPX4 expressions. Thus, reduction decreases protects cardiomyocytes against injury due high glucose. Conclusion This demonstrated could improve suppressing via SIRT1-p53-SLC7A11/GPX4 pathway. may be therapeutic approach management T1DM-induced cardiomyopathy.

Language: Английский

Citations

29
Melatonin suppresses ferroptosis via activation of the Nrf2/HO-1 signaling pathway in the mouse model of sepsis-induced acute kidney injury DOI

Weihuang Qiu,

Sheng An, Tingjie Wang

et al.

International Immunopharmacology, Journal Year: 2022, Volume and Issue: 112, P. 109162 - 109162

Published: Sept. 5, 2022

Language: Английский

Citations

59
Ketogenic diet prevents chronic sleep deprivation-induced Alzheimer’s disease by inhibiting iron dyshomeostasis and promoting repair via Sirt1/Nrf2 pathway DOI Creative Commons

Yueqi Yang,

Xueyan Wang,

Aiai Xiao

et al.

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: Sept. 1, 2022

Sleep deprivation (SD) is one of the main risk factors for Alzheimer's disease (AD), but underlying mechanism still unclear. Ketogenic diet (KD) has been shown widely neuroprotective effects less known about its effect on SD-induced AD. In present study, a continuous 21 days SD mouse model with or without KD was established. The changes cognitive function, pathological hallmarks AD, ferroptosis, and intracellular signal pathways in mice were detected by Morris water maze, ThS staining, diaminobenzidine (DAB)-enhanced Perls' stain, antioxidant assay, immuno-histochemistry, western blot. results showed that can prevent deficiency, amyloid deposition hyperphosphorylated tau induced chronic SD. Analysis ferroptosis revealed inhibit iron dyshomeostasis down-regulating expression TfR1 DMT1 up-regulating FTH1, FPN1. Meanwhile, alleviated oxidative stress elevated xCT/GPX4 axis, FSP1 reduced MDA. addition, could promote neuronal repair enhancing BDNF DCX. Further studies demonstrated activated Sirt1/Nrf2 signaling pathway hippocampus SD-exposed mice. Our finding firstly suggested AD inhibiting improving ability via pathway.

Language: Английский

Citations

42
Asiatic acid alleviates LPS-induced acute kidney injury in broilers by inhibiting oxidative stress and ferroptosis via activation of the Nrf2 pathway DOI
Wenyue Qiu,

Xinting Zhang,

Xiaoyue Pang

et al.

Food and Chemical Toxicology, Journal Year: 2022, Volume and Issue: 170, P. 113468 - 113468

Published: Oct. 14, 2022

Language: Английский

Citations

39
Quercetin alleviates lipopolysaccharide‑induced acute lung injury by inhibiting ferroptosis via the Sirt1/Nrf2/Gpx4 pathway DOI Creative Commons

Shihua Deng,

Jin Li, Li Li

et al.

International Journal of Molecular Medicine, Journal Year: 2023, Volume and Issue: 52(6)

Published: Oct. 20, 2023

Acute lung injury (ALI) causes high morbidity and mortality rates in critically ill patients, there are currently no effective therapeutic drugs. Ferroptosis is a newly discovered mode of regulated cell death that contributes to the progression ALI. Quercetin possesses anti‑inflammatory antioxidant properties. However, whether quercetin can protect against lipopolysaccharide (LPS)‑induced ALI by inhibiting ferroptosis its underlying mechanisms remains unclear. The present study evaluated protective effects molecular LPS‑induced establishing an mouse model alveolar epithelial via treatment mice or cells with LPS. Mouse was assessed evaluating histological score, bronchoalveolar lavage fluid count inflammatory cytokine levels; Cell counting kit‑8, lactate dehydrogenase EDU assays; detecting changes levels malondialdehyde, glutathione, iron, glutathione peroxidase 4 (Gpx4) 4‑hydroxynonenal in vivo vitro. indicated effectively ameliorated reducing histopathological changes, proinflammatory release reactive oxygen species generation ferroptosis. significantly decreased improved proliferative ability LPS‑treated cells. Additionally, it demonstrated markedly enhanced barrier, as evidenced upregulation tight junction protein expression both vitro. Mechanistically, activated sirtuin 1 (Sirt1)/nuclear factor erythroid 2‑related 2 (Nrf2)/Gpx4 signaling pathway, targeted inhibition vitro knockdown Sirt1 reduced anti‑ferroptotic functions quercetin. In conclusion, results exerts activation Sirt1/Nrf2/Gpx4 pathway.

Language: Английский

Citations

35
Paeoniflorin alleviates ischemia/reperfusion induced acute kidney injury by inhibiting Slc7a11-mediated ferroptosis DOI Creative Commons
Lijuan Ma, Xueqi Liu,

Mengya Zhang

et al.

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 116, P. 109754 - 109754

Published: Feb. 6, 2023

The pathophysiological mechanism of acute kidney injury (AKI) is complicated, and effective drugs are still lacking. Ferroptosis a newly discovered regulatory cell death mode characterized by the lethal accumulation iron reactive oxygen species-(ROS-)-dependent lipid hydroperoxides. In recent years, ferroptosis has been confirmed to be involved in progression AKI. Paeoniflorin (PF) traditional Chinese medicine that protective effects on variety diseases including However, which PF attenuates AKI unclear. We detected attenuated serum biochemical markers, histological damage, inflammation dose-dependent manner mouse model with bilateral renal artery ischemia-reperfusion (IR). Hypoxia-reoxygenation (HR)-induced was also inhibited human tubular epithelial cells (HK2). RNA sequence analysis revealed HK2 upregulating Slc7a11 glutathione pathway after HR treatment. failed further protect specific knockdown from under conditions. Consequently, these data indicated prevention requires dependence Slc7a11. This study provided scientific basis for clinical search prevent IR induced

Language: Английский

Citations

32